The Mouse Models Core (Core B) will be responsible for providing the investigators of this Program Project with the tissues and cells necessary to achieve their experimental aims. Experiments in this Program Project focus on mice, both naturally aged mice and a unique strain of mice engineered to age rapidly, which will accelerate the pace of research. Novel strains of double mutant mice, reporter mice, and mice with accelerated aging of one tissue at a time will be bred to address the overarching question- does stochastic, endogenous damage promote aging via a cell autonomous or non-autonomous mechanism? In addition to the genetic approaches, treatment studies will be conducted on mice in Core B to test specific hypotheses about the contribution of oxidative stress, signaling pathways and adult stem cell attrition to aging. By coordinating the creation of animal cohorts and exposure studies within this Core, it will be possible to standardize methods and quality control, which will improve the reproducibility of in vivo experiments, minimize animal use and costs, and dramatically improve the sensitivity of analytical approaches to quantify aging (e.g. histopathology and proteomics). In addition, this centralized Core supports an integrated systems biology approach to the study of aging because all of the following information will be obtained for each animal studied via sharing specimens with each ofthe other projects and cores: Vital statistics, age at onset of aging-related symptoms, organ dysfunction and histopathology: Core B Level of ROS, mitochondrial function, cell death and senescence, identification of cell types affected: Core C Level of oxidative DNA damage: Project 1 Activation of NF-kB and signaling in response to cellular damage and inflammation: Project 2 Adult stem cell function: Project 3